The presence of a passively transferable lethal factor (PTLF) in the blood of animals subjected to irreversible hemorrhagic shock has been controversial. Some investigatorshave described such a factor in dogs and rabbits, but others have failed to confirm this. Further, among those investigators who have found such a toxic factor, there has been disagreement about its nature. Thus, Fine and his colleagues characterized the PTLF as endotoxin while one of us (Nagler) and Zweifach performed experiments which showed the presence of such a factor but showed it not to be biologically active endotoxin. Our goals for this year are: 1. To continue our monitoring of patients in severe protracted shock from traumatic injury, myocardial infarction, surgery and cardiopulmonary bypass to determine the quantitative significance of the presence of the cardiotoxin found in such pateints by bioassay, to develop physical means for its quantitation, and correlate further its presence with the clinical courses of the patients. 2. We will study the physiologic role of the cardiotoxin in shock and determine the mechanism of its action. 3. We will study the route of production and detoxification. The basic aim of our investigation is to identify and determine the significance of the circulating toxic factor(s) we have demonstrated in experimental and human shock syndromes with the view of improving clinical care.